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One Antidepressant Dose Causes Rapid Brain Changes

A single dose of a selective serotonin reuptake inhibitor (SSRI) dramatically and rapidly alters functional connectivity throughout the brain, a new study shows.

Functional magnetic resonance imaging scans of the brains of healthy adults before and after a dose of escitalopram (Lexapro, Forest Laboratories, Inc) revealed changes in connectivity within 3 hours, the study team says.

"We were not expecting the SSRI to have such a prominent effect on such a short timescale or for the resulting signal to encompass the entire brain," Julia Sacher, MD, PhD, of the Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, commented in a news release.

Serotonin is an essential neuromodulator involved in mood regulation. SSRIs are among the most widely studied and prescribed classes of antidepressants, yet it is still not completely clear how they work. They are thought to alter brain connectivity in specific pathways, but those effects had generally been thought to take place during a period of weeks, not hours, the investigators note.

The new findings suggest that changes begin to take place right away and throughout the whole brain.

Dr. Sacher and colleagues measured changes in connectivity in 22 antidepressant-naive and medication-free healthy men and women in their mid-20s in a randomized, double-blind, placebo- controlled crossover study.

Participants underwent 3 resting-state functional magnetic resonance imaging (rs-fMRI) sessions: after a baseline scan, they received either a single oral dose of escitalopram (20 mg) or placebo. Serum levels of escitalopram were determined after 3 hours, after which the participants underwent a second rs-fMRI scan. After an 8-week washout period, the protocol was repeated with the alternate drug.

The researchers found that a single 20-mg dose of escitalopram sparked a widespread decrease in connectivity in most cortical and subcortical areas, with the exception of localized increases in connectivity in cerebellar and thalamic regions.

The findings, say the researchers, "challenge the view that SSRI-induced changes are limited to decreases in connectivity. These findings provide evidence for the particular relevance of serotonin for the modulation of intrinsic brain activity and also demonstrate its unique influence on the cerebello-thalamic tract."

In the placebo condition, no such changes were evident.

The researchers say their findings represent an essential first step toward clinical studies in patients with depression. They plan to compare functional connectivity patterns of brains in recovery and those of patients who fail to respond to SSRI treatment.

Understanding the differences between the brains of individuals who respond to SSRIs and those who do not "could help to better predict who will benefit from this kind of antidepressant vs some other form of therapy," Dr. Sacher said in a news release.

"The hope that we have is that ultimately our work will help to guide better treatment decisions and tailor individualized therapy for patients suffering from depression," she added.

The study was supported by the Society in Science–The Branco Weiss Fellowship. The authors have disclosed no relevant financial relationships